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Polycomb complexes in the repressed state only (
Schwartz et al., 2006
). Inter-
estingly, the Trithorax-component TRX is also constitutively bound to these
PREs (
Papp &Muller, 2006
) and similar co-occupation was detected at many
Polycomb targets loci in
Drosophila
embryos, using ChIP-on-chip
(
Schuettengruber et al., 2009
). Polycomb and Trithorax group components
bind closely neighboring sequences though, as determined in the case of
one
Ubx
PRE. Despite their apparent colocalization, these two protein com-
plexes therefore appear to bind independently from one another (
Tillib et al.,
1999
). An exception to the constitutive binding of these protein complexes is
found at the
Ubx
locus by the Trithorax protein ASH1, which can deposit the
H3K4me3 mark, yet it is not a member of a COMPASS-like complex (
Beisel,
Imhof, Greene, Kremmer, & Sauer, 2002; Schuettengruber et al., 2011
).
ASH1 strongly binds the
Ubx
promoter only when active, whereas its binding
to PREs is still elusive (
Papp & Muller, 2006; Sanchez-Elsner, Gou,
Kremmer, & Sauer, 2006
).
Interestingly,
Drosophila
PREs are depleted in nucleosomes and conse-
quently, they cannot carry H3K27me3 or H3K4me3 marks by themselves
(
Papp & Muller, 2006
). Therefore, they may act as docking platforms for
Polycomb complexes, which would distribute the H3K27me3 mark over
distant
Hox
promoters and gene-bodies. Upon activation, binding of
ASH1 to the
Ubx
promoter, together with TRX bound to the PREs,
may override the H3K27me3-mediated repression, despite the presence
of Polycomb components at PREs (
Papp & Muller, 2006
). However,
how PRC2 is recruited to PREs in
Drosophila
is not yet fully understood
and likely depends upon an intricate cross talk between protein complexes.
While the PhoRC complex indeed displays sequence-specific DNA binding
activity and associates with the PRC2 complex (
Wang, Brown, et al., 2004
),
its binding alone is not sufficient to explain the recruitment of PRC2 to all
targets. Furthermore, PhoRC associates with other protein complexes,
including PRC1 (
Mohd-Sarip, Venturini, Chalkley, & Verrijzer, 2002
).
In the mouse, the distribution of H3K27me3 and H3K4me3 has been
studied at
Hox
loci
in vivo
, during temporal and spatial collinearities
(
Fig. 4.5
C;
Noordermeer et al., 2011; Soshnikova & Duboule, 2009
). Dur-
ing temporal collinear activation, two dynamic and mutually exclusive
domains of histone marks cover the
Hoxd
cluster in the embryonic tailbud.
At an early time point, H3K27me3 marks coat the inactive genes, whereas
H3K4me3 marks are scored over active genes. At a later time point, the
H3K4me3 domain has spread further, coinciding with a shrinking of the
H3K27me3 domain and accompanying the transcriptional activation of
